The purpose of the proposed research program is to gain detailed insight into the mechanisms responsible for ion transport across epithelial tissues, in particular, rabbit colon and gallbladder. The approaches employed will permit us to examine transcellular ion transport in terms of intracellular ionic activities, together with the permselective properties of the apical membrane, the basolateral membrane, and the paracellular shunt pathway. To this end: (a) Electrophysiologic studies will be carried out on rabbit colon in order to define further the mechanism responsible for Na entry across the apical membrane and the regulation of this rate-limiting process; (b) intracellular Cl and K activities in rabbit colonic and gallbladder epithelia will be determined using ion-selective micro-electrodes which have been successfully fabricated in these laboratories in order to define the mechanisms of active Cl absorption and secretion and the relation between intracellular K activities and the electrical potential difference across the basolateral membranes; and (c) the Na-gradient hypothesis for the energization of active Cl secretion by rabbit colon induced by elevations of intracellular cAMP activity will be explored.